The First National Plan to Address Alzheimer's Disease was released in May of 2012 and set a blueprint for research in Alzheimer's disease (AD) to achieve the goal of effective treatment and prevention of the disease by 2025. Toward that end, the Mayo Alzheimer's Disease Research Center (ADRC) is pursuing a program to contribute to that goal. The Center will be comprised of six Cores: Administrative Core to oversee the operations of the Center; Clinical Core to recruit and characterize subjects along the AD spectrum and for the AD-related dementias; Data Management and Statistical Core to collect, refine and analyze data and be compliant with the requirements of the National Alzheimer's Coordinating Center; Neuropathology Core to perform detailed neuropathological studies on autopsy specimens and disseminate genetic and other biospecimens to collaborators; Outreach, Recruitment and Education Core to assist in the recruitment and characterization of subjects for research purposes; and proposed Neuroimaging Core to provide the imaging biomarker data for diagnostic classification and staging of AD and other dementias for research projects and clinical trials on a diverse cohort of ADRC participants across both Mayo Clinic Rochester (MCR) and Mayo Clinic Jacksonville (MCJ) sites. The ADRC also has three research projects including one by a junior investigator. Project 1, Improving Clinical Prediction of Dementia Pathology and Long-Term Outcomes Using Imaging, by Prashanthi Vemuri, Ph.D., will develop a software methodology using clinical and imaging data to predict dementia subtypes; Project 2, Validating HDAC6 as a Novel Therapeutic Target for Alzheimer's Tauopathy, principal investigator Leonard Petrucelli, Ph.D., will validate inhibition of cytosolic histone deacetylase 6 that modulates the accumulation of hyperphosphorylated tau as a possible strategy for the treatment of AD, and Project 3, ApoE Isoforms in Brain Vasculature and CAA, Goujun Bu, Ph.D., will investigate the roles of ApoE and ApoE receptors in the pathogenesis of AD. The ADRC will continue to maintain an active cohort of research subjects and will recruit a new cohort of at-risk subjects for Lewy body disorders. The Center will continue to serve as the nidus for AD research at the Mayo Clinic and will interact with the National Institute on Aging and other Alzheimer's Disease Centers around the country. The Center will remain flexible and adapt to new directions as the field of AD and related dementia research progresses. The purpose of this supplement is to add a Neuroimaging Core to the Mayo Clinic ADRC in order to provide the imaging biomarker data for diagnostic classification and staging of AD and other dementias for research projects and clinical trials on a diverse cohort of ADRC participants across both Mayo Clinic Rochester (MCR) and Mayo Clinic Jacksonville (MCJ) sites. We are proposing a harmonized multi-modality neuroimaging program that would bridge neuroimaging in the MCR and MCJ components of the ADRC, and provide the resources to combine and compare the imaging biomarker data from the African American participants at MCJ with the majority Caucasian participants at MCR. We will establish a tau PET imaging program in the two ADRC sites because tau PET is a novel imaging technology that has the potential to transform the neuroimaging field in AD and other dementias for differential diagnosis, tracking disease progression, selecting subjects for clinical trials and evaluating outcomes. The themes of the Mayo Clinic ADRC propose evaluating patients within the AD spectrum from preclinical to established AD dementia, as well as the non-AD dementias including frontotemporal lobar degeneration (FTLD) and dementia with Lewy Bodies (DLB). Therefore the participants of the Mayo Clinic ADRC both in MCR and MCJ are a rich resource for establishing the imaging features and topographic distribution of tau pathology across the AD spectrum and in non-AD taupathies. It is expected that the Neuroimaging Core will be a catalyst for imaging biomarker studies in the African American populations, aging and dementia cohorts at both sites including tau imaging, that otherwise would not be possible.